Select therapeutics against Connexin 46(Cx46) for treatment of tumors and other hypoxic diseases such as heart disease

Reference Number: K 08-23

Inventors: Nguyen, Annelise; Takemoto, Dolores

Owner: Kansas State University Research Foundation

USPTO Link:

Invention Summary

Researchers at Kansas State University have discovered that the use of certain commercially available compounds to down-regulate a unique gap junction protein, Connexin 46 (Cx46), could potentially be used to treat certain cancers and other hypoxic diseases such as heart disease.

Cx46 plays an important role in the survival of hypoxic tissues. Hypoxia is a deficiency of oxygen and normal tissues undergo programmed cell death when oxygen reaches low levels. The lens of the eye is the only naturally occurring hypoxic tissue in the human body and the lens is usually the only tissue where Cx46 is found. Drs. Nguyen and Takemoto collaborated to show that breast cancer also expresses Cx46, thus, in general, human tissues which are hypoxic express Cx46. In vitro work showed that when Cx46 is down-regulated with certain commercially available therapeutic compounds, the cells would die at low oxygen levels showing that the targeted down-regulation of Cx46 can be used therapeutically to cause hypoxic tissues such as tumors to die.

In addition, the increase in Cx46 causes a decrease in Cx43, a gap junction protein which is required for normal cell growth and control. Specifically, Cx43 is critical for normal synchronization of cardiac myofibrils. Diseased hearts have a loss of Cx43 due to transient hypoxia. Thus, down-regulation of Cx46 can also be used to treat heart disease.

Advantages

• The first to describe the use of select therapeutics to down-regulate Cx46 for treating hypoxic diseases

• The first to describe an increase in Cx46 during hypoxia drives the loss of Cx43

• Current strategies directed at another protein associated with hypoxia, HIF-1α have shown many side effects as this is broadly found in all cells and is a common gene regulator.

Applications

• Treatment of tumors

• Treatment of acute or chronic heart disease

• Treatment of retinal ischemia

• Treatment of brain ischemia either transient or during stroke

• Animal health applications